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Int J Radiat Oncol Biol Phys. 2016 Apr 1;94(5):1173-80. doi: 10.1016/j.ijrobp.2015.12.367. Epub 2015 Dec 29.

High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma.

Author information

1
Department of Radiation Oncology, Columbia University Medical Center, New York, New York.
2
Department of Surgery, Columbia University Medical Center, New York, New York.
3
Department of Pediatrics, Columbia University Medical Center, New York, New York.
4
Department of Surgery, University of Chicago, Chicago, Illinois.
5
Department of Surgery, Columbia University Medical Center, New York, New York; Department of Pediatrics, Columbia University Medical Center, New York, New York; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
6
Department of Radiation Oncology, Columbia University Medical Center, New York, New York. Electronic address: epc2116@cumc.columbia.edu.

Abstract

PURPOSE:

To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)-pericyte interaction as a potential target for combined treatment with antiangiogenic agents.

METHODS AND MATERIALS:

The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed.

RESULTS:

HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours.

CONCLUSIONS:

HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

PMID:
26907918
DOI:
10.1016/j.ijrobp.2015.12.367
[Indexed for MEDLINE]

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